Vitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis

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dc.contributor.authorMesnard, Laurent
dc.contributor.authorRafat, Cedric
dc.contributor.authorVandermeersch, Sophie
dc.contributor.authorHertig, Alexandre
dc.contributor.authorCathelin, Dominique
dc.contributor.authorXu-Dubois, Yi-Chun
dc.contributor.authorJouanneau, Chantal
dc.contributor.authorKeller, Alexandre Castro [UNIFESP]
dc.contributor.authorRibeil, Jean-Antoine
dc.contributor.authorLeite-de-Moraes, Maria C.
dc.contributor.authorRondeau, Eric
dc.contributor.institutionUniv Paris 06
dc.contributor.institutionHop Necker Enfants Malad
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.date.accessioned2016-01-24T14:17:14Z
dc.date.available2016-01-24T14:17:14Z
dc.date.issued2011-10-01
dc.description.abstractDuring human glomerulonephritis, the severity of injuries correlates with glomerular fibrin deposits, which are tightly regulated by the intraglomerular fibrinolytic system. Here, we evaluated the role of vitronectin (VTN; also known as complement S protein), the principal cofactor of the plasminogen activator inhibitor-1 (PAI-1), in a mouse model of acute glomerulonephritis. We found that in mice subjected to nephrotoxic serum, the absence of VTN resulted in a lower glomerular PAI-1 activity and a higher glomerular fibrinolytic activity. Challenged VTN-/- mice displayed significantly less fibrin deposits, proteinuria, and renal failure than their wild-type counterparts. Notably, this protective effect afforded by VTN deficiency was still observed after a C3 depletion. Finally, the injection of VTN+/+ serum in VTN-/- mice induced the glomerular deposition of VTN, increased PAI-1 deposition, decreased glomerular fibrinolytic activity, and aggravated glomerular injury. As in mice, abundant glomerular VTN deposits were also observed in patients with severe glomerulonephritis. Here, we show that plasma-exchange therapy, admittedly beneficial in this clinical context, induces a significant depletion in circulating VTN, which might modulate PAI-1 activity locally and accelerate the clearance of fibrin deposits in the glomeruli. Collectively, these results demonstrate that VTN exerts a deleterious role independently from complement, by directing PAI-dependent fibrinolysis in the glomerular compartment.-Mesnard, L., Rafat, C., Vandermeersch, S., Hertig, A., Cathelina, D., Xu-Dubois, Y. -C., Jouanneau, C., Castro Keller, A., Ribeil, J. -A., Leite-de-Moraes, M. C., Rondeau, E. Vitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritis. FASEB J. 25, 3543-3553 (2011). www.fasebj.orgen
dc.description.affiliationUniv Paris 06, INSERM, UMR S702, Hop Tenon, F-75020 Paris, France
dc.description.affiliationUniv Paris 06, Hop Tenon, APHP, F-75020 Paris, France
dc.description.affiliationHop Necker Enfants Malad, CNRS, UMR 8147, Paris, France
dc.description.affiliationHop Necker Enfants Malad, APHP, Fac Med Rene Descartes, Dept Biotherapie, Paris, France
dc.description.affiliationUniversidade Federal de São Paulo, Div Nephrol, São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Nephrol, São Paulo, Brazil
dc.description.sourceWeb of Science
dc.description.sponsorshipInstitut National de la Sante et de la Recherche Medicale (INSERM)
dc.description.sponsorshipFaculte de Medecine Pierre et Marie Curie
dc.description.sponsorshipAcademie de Medecine
dc.description.sponsorshipEuropean Renal Association-European Dialysis and Transplant Association (ERA-EDTA)
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorshipConselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.description.sponsorshipIDFAPESP: 2007/07120-0
dc.description.sponsorshipIDCNPq: 501848/2009-6
dc.format.extent3543-3553
dc.identifierhttp://dx.doi.org/10.1096/fj.11-180752
dc.identifier.citationFaseb Journal. Bethesda: Federation Amer Soc Exp Biol, v. 25, n. 10, p. 3543-3553, 2011.
dc.identifier.doi10.1096/fj.11-180752
dc.identifier.issn0892-6638
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34073
dc.identifier.wosWOS:000295356400024
dc.language.isoeng
dc.publisherFederation Amer Soc Exp Biol
dc.relation.ispartofFaseb Journal
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectcomplement systemen
dc.subjectmouse modelen
dc.subjectPAI-1en
dc.subjectKidneyen
dc.titleVitronectin dictates intraglomerular fibrinolysis in immune-mediated glomerulonephritisen
dc.typeinfo:eu-repo/semantics/article
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